Human soluble CD80 is generated by alternative splicing, and recombinant soluble CD80 binds to CD28 and CD152 influencing T-cell activation
Human soluble CD80 is generated by alternative splicing, and recombinant soluble CD80 binds to CD28 and CD152 influencing T-cell activation
复制标题
DOI：
10.1111/j.1365-3083.2007.02009.x
复制
发表时间：
2007-11-01
影响因子：
3.7
通讯作者：
Wang, X.
中科院分区：
文献类型：
--
作者：
Kakoulidou, M.;Giscombe, R.;Wang, X.
CD 80是一种共刺激因子，主要表达于活化的单核细胞、B细胞和树突状细胞表面。在这项研究中，我们证明，24%的健康人有可溶性形式的CD 80，sCD 80，在他们的血清中。sCD 80的浓度范围为0至1 mg/l。在mRNA水平，我们检测到一个剪接形式s1 CD 80（771 bp），在未刺激的单核细胞和B细胞，而另一种形式命名为s2 CD 80（489 bp）的表达在活化的T细胞以及新鲜分离和活化的单核细胞。s1 CD 80缺乏跨膜结构域，而s2 CD 80的IgC样结构域和跨膜结构域被剪切掉。我们还提供的数据表明，重组s1 CD 80结合重组CD 152-IG和CD 28-IG。它还可以结合T细胞，优先结合活化的T细胞。重组sCD 80具有免疫调节作用，表现为抑制混合淋巴细胞反应和抑制T细胞增殖。人血清中的sCD 80为可溶性受体家族增加了一个新成员，这意味着具有功能相关性的可溶性共刺激因子网络。重组蛋白对T细胞活化的抑制作用使其成为治疗与过度活化的T细胞相关的疾病的可能候选物。
CD80 is a costimulatory factor mainly expressed on the surface of activated monocytes, B cells and dendritic cells. In this study, we demonstrate that 24% of healthy individuals have soluble forms of CD80, sCD80, in their serum. The concentration of sCD80 ranged from 0 to 1 mg/l. At the mRNA level, we detected a spliced form s1CD80 (771 bp), in unstimulated monocytes and B cells, while another form named s2CD80 (489 bp) was expressed in activated T cells as well as in freshly isolated and activated monocytes. s1CD80 lacks the transmembrane domain, and the IgC-like domain plus the transmembrane domain are spliced out of s2CD80. We also present data demonstrating that recombinant s1CD80 binds to recombinant CD152-Ig and CD28-Ig. It can also bind to T cells, preferentially to activated T cells. Recombinant sCD80 had immunomodulatory effects shown by its inhibition of the mixed lymphocyte reaction and inhibition of T-cell proliferation. sCD80 in human serum adds a new member to the family of soluble receptors, implying a network of soluble costimulatory factors with functional relevance. The inhibitory effect of the recombinant protein on T-cell activation makes it a possible candidate for treatment of diseases associated with hyperactivated T cells.